Antibodies against the various pathogenic serotypes of pneumococcal capsular polysacharides (PnPs) provide protection from infection , but pure PnPs are T cell independent antigens and are poor immunogens in children and elderly. Conjugation of PnPs to a carrier protein improves the PnPs-specific antibody (Ab) response and elicits T cell help. The experimental pneumococcal-protein conjugate vaccine uses purified PnPs-specific B cell precursors or whether it is due to the effect of the serotype of the PnPs-specific B cell precursors or whether it is due to the effect of the serotype off the PnPs on the antigen processing of CRM197 yielding alterations in subsequent T cell help in humans. We will immunize fifty adult volunteers with the experimental 7 valent PnPs- CRM/197 vaccine and measure Ab levels against each serotype as well as CRM/197. We will also determine if donor peripheral CD4+ T cells specific for certain CRM/197 epitopes are associated with better immunogenicity of PnPs. Next, we will examine the frequency of PnPs- specific B cell precursors in each donor and determine if PnPs-specific B cell frequency correlates with PnPs Ab titer. We will also determine if PnPs antibody V region gene usage is different for low responder serotypes. Finally, we will examine whether the serotype of PnPs affects processing and presentation of carrier protein-derived epitopes by human antigen processing cells, yielding differences in subsequent T cell help. These data will significantly add to our understanding of the immune response to conjugate vaccines and may provide information useful to the design of second-generation vaccines.